Methods and reagents for regulating apoptosis
OwnerGrant McFadden, Michael Moraninventors
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Abstract
The present invention relates to methods and reagents useful for inhibition of apoptosis. Specifically, the invention relates to methods to identify agents that is either pro-apoptotic or anti-apoptotic, especially by affecting the signal transduction pathways of BAK protein and/or M11L protein. The invention also provides business methods, diagnostic kits for identification of pro- or anti-apoptotic agents. Another aspect of the invention provides a method to identify M11L-interacting polypeptides using mass spectrometry.
Claims37
A method for identifying agents which may be potentially pro-apoptotic or anti-apoptotic, comprising:
- A) providing a reaction mixture including complexes of BAK and/or M11L proteins;
- B) contacting the reaction mixture with one or more test agents;
- C) determining if the test agent possesses at least one of the following abilities:
- 1) binding to the complex;
- 2) increasing or decreasing the steady state level of the complex;
- 3) affecting an enzymatic activity of the complex;
- 4) affecting a subcellular localization of the complex.
The method of 8, wherein step D) is carried out in vivo or in whole cells.
A method of conducting a drug discovery business comprising:
- A) providing one or more assay systems for identifying agents by their ability to inhibit or potentiate BAK-dependent and/or M11L-dependent apoptosis;
- B) conducting therapeutic profiling of agents identified in step A), or further analogs thereof, for efficacy and toxicity in animals;
- and
- C) formulating a pharmaceutical preparation including one or more agents identified in step (B) as having an acceptable therapeutic profile.
A method of conducting a target discovery business comprising:
- A) providing one or more assay systems for identifying agents by their ability to inhibit or potentiate BAK-dependent and/or M11L-dependent apoptosis;
- B) (optionally) conducting therapeutic profiling of agents identified in step A) for efficacy and toxicity in animals;
- and
- C) licensing, to a third party, the rights for further drug development and/or sales for gents identified in step A), or analogs thereof.
A method to identify M11L-interacting polypeptides, comprising:
- A) contacting M11L with a reaction mixture;
- B) retrieving M11L, together with any M11L-interacting polypeptides, from the reaction mixture;
- C) identifying M11L-interacting polypeptides of B) using mass spectrometry.
Dependencies are inferred from the claim text.